Involvement of 3',5'-cyclic adenosine monophosphate-dependent protein kinase in regulation of Fos expression and tyrosine hydroxylase levels during morphine withdrawal in the hypothalamic paraventricular nucleus and medulla oblongata catecholaminergic cell groups
| Autor: | M. Luisa Laorden, M. Victoria Milanés, Marta Benavides |
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| Rok vydání: | 2005 |
| Předmět: |
Male
Narcotics medicine.medical_specialty Tyrosine 3-Monooxygenase Narcotic Antagonists Blotting Western (+)-Naloxone Biochemistry Rats Sprague-Dawley Cellular and Molecular Neuroscience Catecholamines Internal medicine medicine Solitary Nucleus Animals Protein kinase A Protein Kinase Inhibitors Drug Implants Neurons Medulla Oblongata Sulfonamides Tyrosine hydroxylase Morphine Chemistry Solitary nucleus Isoquinolines Cyclic AMP-Dependent Protein Kinases Rats Substance Withdrawal Syndrome Disease Models Animal Endocrinology nervous system Gene Expression Regulation Hypothalamus Medulla oblongata Catecholaminergic cell groups Morphine Dependence Proto-Oncogene Proteins c-fos medicine.drug Paraventricular Hypothalamic Nucleus |
| Zdroj: | Journal of neurochemistry. 92(2) |
| ISSN: | 0022-3042 |
| Popis: | Morphine withdrawal stimulates the hypothalamic-pituitary-adrenocortical axis activity by activation of nucleus tractus solitarius (NTS)/ventrolateral medulla (VLM) noradrenergic pathways innervating the hypothalamic paraventricular nucleus (PVN). We investigated whether cAMP-dependent protein kinase (PKA) plays a role in this process by estimating changes in PKA immunoreactivity and the influence of inhibition of PKA on Fos protein expression and tyrosine hydroxylase (TH) immunoreactivity levels in the PVN and NTS/VLM during morphine withdrawal. Dependence on morphine was induced by a 7-day s.c. implantation of morphine pellets. Morphine withdrawal was precipitated on day 8 by an injection of naloxone (5 mg/kg s.c.). When opioid withdrawal was precipitated, an increase in PKA immunoreactivity levels was observed 90 min after naloxone administration in the PVN and NTS/VLM areas. Morphine withdrawal induced expression of Fos in the PVN and NTS/VLM, indicating an activation of neurones in those nuclei. TH immunoreactivity in NTS/VLM was increased 90 min after induction of morphine withdrawal, whereas there was a decrease in TH levels in the PVN at the same time point. When the selective PKA inhibitor HA-1004 was infused it greatly diminished the Fos expression observed in morphine-withdrawn rats. Furthermore, the changes in TH immunoreactivity were significantly modified by infusion of HA-1004. The present findings suggest that an up-regulated PKA-dependent transduction pathway might contribute to the activation of the hypothalamic-pituitary-adrenocortical axis in response to morphine withdrawal. |
| Databáze: | OpenAIRE |
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